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Glucagon-like Peptide-1 Receptor Agonists and Cardioprotective Benefit in Patients with Type 2 Diabetes Without Baseline Metformin: A Systematic Review and Update Meta-analysis

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Abstract

Introduction

Sodium Glucose Co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs) were associated with a reduction in cardiovascular disease events in cardiovascular outcomes trials (CVOTs) in type 2 diabetes. Most of the patients included in these trials received metformin as background therapy.

Aim

To evaluate the effect of glucagon-like peptide 1 receptor agonists on major cardiovascular events (MACE) and mortality in metformin-naïve patients with type 2 diabetes.

Methods

A systematic review and meta-analysis of randomized controlled clinical trials of GLP-1RAs on type 2 diabetes population was performed, after searching the PubMed/MEDLINE, Embase, Scielo, Google Scholar and Cochrane Controlled Trials databases. The primary endpoint was MACE. The secondary endpoints were cardiovascular death and all-cause mortality. A meta-analysis of time-to-event outcomes was performed. This meta-analysis was registered in PROSPERO (CRD42021260040)

Results

Seven trials, including 11510 patients, were identified and considered eligible for the analyses. GLP-1RAs were associated with a significant reduction in MACE incidence (HR: 0.86, 95% confidence interval: 0.79–0.94; I2: 0%). The secondary endpoints analysis showed a non-significant reduction in all-cause mortality (HR: 0.86, 95% confidence interval: 0.73–1.00 I2: 0%) and cardiovascular mortality (HR: 0.81, 95% confidence interval: 0.63–1.05; I2: 0%).

Conclusions

In this meta-analysis, GLP-1RAs reduced the incidence of MACE in patients with type 2 diabetes without metformin at baseline, without significant reduction in all-cause mortality and cardiovascular mortality. These results support the fact that when a GLP-1RAs is administered, the benefit on cardiovascular outcomes is independent of the use of metformin.

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Authors and Affiliations

  1. Council of Epidemiology and Cardiovascular Prevention, Argentine Society of Cardiology, Azcuenaga 980, Buenos Aires, Argentina

    Augusto Lavalle-Cobo, Walter Masson, Martín Lobo, Gerardo Masson & Graciela Molinero

  2. Cardiology Department, Sanatorio Finochietto, Av. Córdoba 2678, Buenos Aires, Argentina

    Augusto Lavalle-Cobo, Walter Masson, Martín Lobo & Gerardo Masson

  3. Cardiology Department, Hospital Italiano de Buenos Aires. Tte. Gral, Juan Domingo Perón 4190, Buenos Aires, Argentina

    Walter Masson, Martín Lobo & Gerardo Masson

  4. Cardiology Department, Hospital Militar Campo de Mayo. Tte. Gral. Ricchieri S/N, Buenos Aires, Argentina

    Martín Lobo & Gerardo Masson

  5. Cardiology Department, Instituto Cardiovascular San Isidro-Sanatorio Las Lomas, Von Wernicke 3031, San Isidro, Argentina

    Gerardo Masson

  6. 926 7B, Ayacucho, Argentina

    Augusto Lavalle-Cobo

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  1. Augusto Lavalle-Cobo
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Contributions

ALC was the main coordinator of the project and was responsible for the study design. ALC and WM drafted the manuscript of the present paper. ML was involved in the supervising of data collection and stratification. ML and GM contributed to data assembly and analysis. GM contributed with manuscript revision. All authors contributed intellectually to this manuscript and have approved this final version.

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Correspondence to Augusto Lavalle-Cobo.

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Augusto Lavalle Cobo has received honoraria from Novo Nordisk.

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Lavalle-Cobo, A., Masson, W., Lobo, M. et al. Glucagon-like Peptide-1 Receptor Agonists and Cardioprotective Benefit in Patients with Type 2 Diabetes Without Baseline Metformin: A Systematic Review and Update Meta-analysis. High Blood Press Cardiovasc Prev 28, 605–612 (2021). https://doi.org/10.1007/s40292-021-00479-1

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